Toxicological Sciences最新文献

{"title":"Investigation of Urinary miRNA Profile Changes in Amphotericin B-Induced Nephrotoxicity in C57BL/6 Mouse, Sprague-Dawley Rats and Beagle Dogs.","authors":"Adeyemi O Adedeji, Michael R Tackett, Genesis Tejada, James E McDuffie","doi":"10.1093/toxsci/kfaf029","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf029","url":null,"abstract":"<p><p>MicroRNA (miRNAs) have been associated with drug-induced kidney injury (DIKI). However, there are few reports on the utility of miRNAs, when monitoring for nephrotoxicity across multiple species. The purpose of this study was to assess the value of urinary miRNA profile changes as renal safety biomarkers, when monitoring for kidney injury in investigative toxicology studies. To this end, we evaluated urine miRNA expression levels in response to amphotericin B (AmpB-induced nephrotoxicity in mice, rats and dogs. The results showed that 35 miRNAs were significantly differentially expressed across the three species in response to the induced renal injuries. Dogs showed the highest number of miRNAs with significant changes. miR-205-5p and miR-31-5p were the most consistently altered miRNA biomarkers across all three species. In rodents, these two miRNAs were the most sensitive markers and showed comparable or better sensitivities than the previously published urine protein biomarkers with the same nephrotoxicant. In dogs, none of the upregulated miRNAs were as sensitive as urine clusterin protein as observed in a previously published study with AmpB. Taken together, these miRNAs could complement the more established urinary protein biomarkers in monitoring DIKI in mice, rats and dogs. To our knowledge, this is the first report that demonstrates the comparative utility of urinary miRNAs for the early detection of DIKI across three nonclinical animal models.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling the developing nervous system: a neuroscience perspective on the use of NAMs in DNT testing.","authors":"Andrew J Newell, Heather B Patisaul","doi":"10.1093/toxsci/kfaf028","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf028","url":null,"abstract":"<p><p>There is widespread concern that environmental exposures constitute an underappreciated but significant contribution to rising rates of neurodevelopmental disorders (NDDs). There is also international consensus that regulatory frameworks for developmental neurotoxicity (DNT) testing are woefully inadequate, prompting reappraisal of DNT testing methods. One approach aims to make testing more efficient, less animal-intensive, and higher throughput, through in vitro evaluation of DNT. These new approach methodologies (NAMs) promise to accelerate and standardize DNT testing through interrogation of fundamental mechanisms of neurodevelopment. While in the early stages of development, they have significant, well-publicized shortcomings, including little to no accounting for cellular or genetic diversity, cell extrinsic signaling molecules, sex as a biological variable, developmental stage, or relevance to NDDs. One of the most advanced NAM platforms is a collection of 17 in vitro assays termed the DNT in vitro battery (IVB). While it models some aspects of neurodevelopmental processes, it fails to capture others. Proper brain ontogeny, and consequently normal behavior and cognition, relies on the integrity of fundamental mechanisms, their temporal/spatial fidelity, and the magnitude of their expression. These fundamental mechanisms are regulated by factors not considered by the DNT IVB including diverse cell types and neurotransmitters. While the DNT IVB could prove to be an important tool in DNT hazard detection, we identify key areas, including cell-extrinsic neurotransmitter signaling, diversity of neural progenitors, interneurons, and biological sex, that should be prioritized for development and inclusion in future refinements to meaningfully enhance biological coverage and relevance to human cognition and behavior.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential hepatic activation of mouse and human peroxisome proliferator-activated receptor-α by perfluorohexane sulfonate.","authors":"Yahya Khan, Annalee M Schmidt, Kyle J Oldro, Xiaoyang Zhu, Angelina R Kramer, Sarah R Hamilton, Katherine O Bleil, Ryan M Krisko, Jeremiah D Zitzow, Yuan Tian, Shu-Ching Chang, Vonn Walter, Samuel M Cohen, Frank J Gonzalez, Andrew D Patterson, Jeffrey M Peters","doi":"10.1093/toxsci/kfaf026","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf026","url":null,"abstract":"<p><p>Exposure of perfluorohexane sulfonate (PFHxS) is associated with hepatomegaly and accumulation of lipids that may be mediated by nuclear receptors like peroxisome proliferator-activated receptor-α (PPARα), constitutive androstane receptor (CAR), or pregnane X receptor (PXR). This study tested the hypotheses that: 1) PFHxS causes changes in liver by activating PPARα, CAR or PXR, and 2) there is a species difference in PPARα activity by PFHxS. Wild-type, Ppara-null, and PPARA-humanized mice were fed either a control diet, or one containing 2.2 mg PFHxS/kg diet or 25.8 mg PFHxS/kg diet for either seven or twenty-eight days, and target gene expression was examined. Relative liver weights were similar after seven days with either 2.2 or 25.8 mg PFHxS/kg dietary exposure compared to controls. Relative liver weights were higher after treatment for twenty-eight days in all three genotypes fed 25.8 mg PFHxS/kg diet compared to controls. The concentration of PFHxS was dose-dependently increased in serum and liver compared to controls. PFHxS exposure of 2.2 and 25.8 mg PFHxS/kg diet caused an increase in expression of PPARα target genes in wild-type mice and this effect was not observed in similarly treated Ppara-null mice or PPARA-humanized mice. Administration of PFHxS caused increased expression of the CAR target gene Cyp2b10 in all three genotypes at both timepoints, and the PXR target gene Cyp3a11 in all three genotypes after twenty-eight days. Exposure to PFHxS can increase liver weight due in part to the activation of mouse, but not human, PPARα. Activation of CAR and PXR by PFHxS also likely contributes to the observed hepatomegaly in all three genotypes.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast Cells are Key Mediators in the Pulmonary Inflammatory Response to Formaldehyde Exposure.","authors":"Matthew Gibb, Angela N Reinert, Troy Schedin, Daniel T Merrick, Jared M Brown, Alison K Bauer","doi":"10.1093/toxsci/kfaf025","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf025","url":null,"abstract":"<p><p>Formaldehyde (FA) is a common chemical linked to respiratory problems such as airway hyperresponsiveness and pulmonary inflammation. Due to its toxicological effects and ease of mass production, FA is also recognized as a significant chemical threat by the U.S. Department of Homeland Security. This study investigates the role of mast cells in the pulmonary inflammatory response to acute high dose FA exposure. Using wild type (C57BL/6J) and mast cell-deficient (KitW-sh) mouse models, we assessed the impact of oropharyngeal aspiration of FA on lung pathology. Our findings reveal that C57BL/6J mice experienced significant increases in cellular infiltration, altered immune cell populations, and changes in lipid mediator profiles. In contrast, KitW-sh mice exhibited significantly reduced inflammatory responses. Notably, the presence of mast cells was associated with enhanced dendritic cell migration and differential production of bioactive lipid mediators, such as specialized pro-resolving mediators and pro-inflammatory leukotrienes in C57BL/6J mice. These results highlight the crucial role of mast cells in the immune response to formaldehyde and suggest they could be therapeutic targets for treating FA-induced lung inflammation.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLKL deficiency exacerbates early injury in a mouse model of acetaminophen hepatotoxicity.","authors":"Giselle Sanchez-Guerrero, David S Umbaugh, Sawyer H Smith, Jephte Y Akakpo, Hartmut Jaeschke, Anup Ramachandran","doi":"10.1093/toxsci/kfaf022","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf022","url":null,"abstract":"<p><p>An overdose of acetaminophen (APAP) is the leading cause of drug-induced hepatotoxicity and acute liver failure (ALF) in the United States. It is established that the predominant mode of hepatocyte cell death after an APAP overdose is through necrosis, and it is now recognized that this occurs through regulated pathways involving RIP kinases. These kinases, along with the pseudo-kinase MLKL are central players in classical necroptotic cell death. Despite the skepticism regarding the role of necroptosis in APAP-induced liver injury, recent research demonstrating necroptosis-independent roles for MLKL led us to re-examine the role of this pseudo-kinase in APAP pathophysiology. Treatment of Mlkl-/-mice with a moderate (300 mg/kg) overdose of APAP resulted in an exacerbation of liver injury at 6- and 12-hours post-APAP as evidenced by elevated plasma alanine aminotransferase activities, and extensive necrosis accompanied by diminished glutathione levels. Interestingly, these differences between Mlkl-/- and wild type mice were negated at the 24-hour mark, previously scrutinized by others. At 6 and 12 hours post APAP, Mlkl-/- mice exhibited augmented translocation of AIF and Endonuclease G without affecting JNK activation, suggesting enhanced mitochondrial permeability transition in the absence of MLKL. Lack of MLKL also impacted autophagy, the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, with decreased levels of p62 and LC3B and increased expression of CHOP and GRP78 at 6 hours post APAP. In essence, our findings illuminate a noncanonical role for MLKL in the early phases of APAP-induced liver injury, warranting further exploration of its influence on APAP pathophysiology.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR in Placental Health and Disease: Pathways, Dysfunction, and Chemical Disruption.","authors":"Anita A Waye, Jacob Moeller, Almudena Veiga-Lopez","doi":"10.1093/toxsci/kfaf024","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf024","url":null,"abstract":"<p><p>Formation of the placenta during gestation is required to support fetal growth and development. Derived from the placenta, trophoblast cells express nuclear and membrane-bound receptors. Among these receptors is the epidermal growth factor receptor (EGFR) which plays a key role in placental development. Activation of EGFR-mediated signaling in trophoblast cells regulates critical processes, such as proliferation, differentiation, invasion, and fusion during pregnancy, making it essential for normal placental formation. Dysfunction of EGFR in placental trophoblast cells has been associated with adverse pregnancy outcomes, including intrauterine growth restriction, preeclampsia, and preterm birth. Ubiquitous environmental chemicals, like polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorine pesticides, and bisphenols, have been reported to modulate EGFR signaling pathways, potentially contributing to placental dysfunction. This review explores the pivotal role of EGFR signaling in placental development and function, with a focus on how environmental chemicals interfere with EGFR-mediated pathways and placental cell functions as well as their implications for pregnancy outcomes. Findings presented herein underscore the need for further research into the effects of exposure to environmental chemicals on modulating EGFR signaling pathways in the context of placental health.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-specific variation in per- and polyfluoroalkyl substances toxicity among genetically diverse Caenorhabditis elegans strains.","authors":"Tess C Leuthner, Sharon Zhang, Brendan F Kohrn, Heather M Stapleton, L Ryan Baugh","doi":"10.1093/toxsci/kfaf014","DOIUrl":"10.1093/toxsci/kfaf014","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are in 99% of humans and are associated with a range of adverse health outcomes. It is impossible to test the >14,500 structurally diverse \"forever chemicals\" for safety, therefore improved assays to quantify structure-activity relationships are needed. Here, we determined the toxicity of a structurally distinct set of PFAS in twelve genetically diverse strains of the genetic model system Caenorhabditis elegans. Dose-response curves for perfluoroalkyl carboxylic acids (PFNA, PFOA, PFPeA, and PFBA), perfluoroalkyl sulfonic acids (PFOS and PFBS), perfluoroalkyl sulfonamides (PFOSA and PFBSA), fluoroether carboxylic acids (GenX and PFMOAA), fluoroether sulfonic acid (PFEESA), and fluorotelomers (6:2 FTCA and 6:2 FTS) were determined in the C. elegans laboratory reference strain, N2, and eleven genetically diverse wild strains. Body length was quantified after 48 hr of developmental exposure of L1 arrest-synchronized larvae to estimate effective concentration values (EC50). PFAS toxicity ranged by three orders of magnitude. Long-chain PFAS had greater toxicity than short-chain and fluorosulfonamides were more toxic than carboxylic and sulfonic acids. Genetic variation resulted in variation in susceptibility among twelve strains to almost all chemicals. Different C. elegans strains varied in susceptibility to different PFAS, which suggests distinct molecular responses to specific structural attributes. Harnessing the natural genetic diversity of C. elegans and the structural complexity of PFAS is a powerful approach that can be used to investigate mechanisms of toxicity which may identify potentially susceptible individuals or populations and predict toxicity of untested PFAS to inform regulatory policies and improve human and environmental health.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons learned from evaluating defined chemical mixtures in a high throughput estrogen receptor assay system.","authors":"Fred Parham, Kristin M Eccles, Cynthia V Rider, Srilatha Sakamuru, Menghang Xia, Ruili Huang, Raymond R Tice, Gregg E Dinse, Michael J Devito","doi":"10.1093/toxsci/kfaf020","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf020","url":null,"abstract":"<p><p>In this paper, we provide a proof of concept evaluating the utility of the U.S. Tox21 high-throughput screening approach to assess the hazard of chemical mixtures using two estrogen receptor assays. A subset of chemicals identified in Phase I of the Tox21 program as active in the estrogen receptor (ER) agonist assay were used to design mixtures for testing in Phase II. Individual chemicals and mixtures were evaluated in two cell-based estrogen receptor alpha (ERα) activation assays: One incorporating a transfected ligand-binding domain in an ERα β-lactamase reporter cell line (ER-bla) and the full-length endogenous receptor in the MCF7 cell line with a luciferase reporter gene (ER-luc). Concentration-response data from individual chemicals were used to predict the joint effect based on mixtures modeling methods and were compared to observed mixtures data to assess model fit. The models tended to overpredict mixture responses in the ER-bla assay, while predictions were closer to observed responses in the ER-luc assay, indicating that a full-length endogenous estrogen receptor is a preferred model for high-throughput mixture analysis. Lessons learned from this research include the importance of analyzing the individual chemicals used for predictions and the mixtures in the same experimental paradigm to minimize variation, developing methods for imputing missing values from incomplete concentration-response curves, and establishing criteria to determine when inactive chemicals should be omitted from mixture predictions.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of New Approach Methods for the Assessment of Data Poor Chemicals.","authors":"Katie Paul Friedman, Russell S Thomas, John F Wambaugh, Joshua A Harrill, Richard S Judson, Timothy J Shafer, Antony J Williams, Jia-Ying Joey Lee, Lit-Hsin Loo, Matthew Gagné, Alexandra S Long, Tara S Barton-Maclaren, Maurice Whelan, Mounir Bouhifd, Mike Rasenberg, Ulla Simanainen, Tomasz Sobanski","doi":"10.1093/toxsci/kfaf019","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf019","url":null,"abstract":"<p><p>Use of new approach methods (NAMs), including high-throughput, in vitro bioactivity data, in setting a point-of-departure (POD) will accelerate the pace of human health hazard assessments. Combining hazard and exposure predictions into a bioactivity: Exposure ratio (BER) for use in risk-based prioritization and utilizing NAM-based bioactivity flags to indicate potential hazards of interest for further prediction or mechanism-based screening together comprise a prospective approach for management of substances with limited traditional toxicity testing data. In this work we demonstrate a NAM-based assessment case study conducted via the Accelerating the Pace of Chemical Risk Assessment (APCRA) initiative, a consortium of international research and regulatory scientists. The primary objective was to develop a reusable and adaptable approach for addressing chemicals with limited traditional toxicity data using a NAM-based POD, BER, and bioactivity-based flags for indication of putative endocrine, developmental, neurological, and immunosuppressive effects via data generation and interpretation for 200 substances. Multiple data streams, including in silico and in vitro NAMs, were used. High-throughput transcriptomics and phenotypic profiling data, as well as targeted biochemical and cell-based assays, were combined with generic high-throughput toxicokinetic models parameterized with chemical-specific data to estimate dose for comparison to exposure predictions. This case study further enables regulatory scientists from different international purviews to utilize efficient approaches for prospective chemical management, addressing hazard and risk-based data needs, while reducing the need for animal studies. This work demonstrates the feasibility of using a battery of toxicodynamic and toxicokinetic NAMs to provide a NAM-based POD for screening-level assessment.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis identifies muscle-specific mitochondrial and vesicular transport genes as methylmercury toxicity targets in a Drosophila model of Congenital Minamata Disease.","authors":"Catherine R Beamish, Jennifer Becker, Lok Ming Tam, Tanzy Love, Matthew D Rand","doi":"10.1093/toxsci/kfaf018","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf018","url":null,"abstract":"<p><p>Prenatal methylmercury (MeHg) exposure presents a heightened concern in early human development, as has been exemplified in historic cases of Congenital Minimata Disease (CMD). Children that experience CMD characteristically present with various degrees of cognitive and motor symptoms and signs, much like cerebral palsy. MeHg has thus been characterized as a neurotoxicant, where motor deficits are ascribed to central nervous system targets. Skeletal muscle as a post-synaptic MeHg target and contributor to the etiology of CMD has garnered far less attention. Prior studies using Drosophila to model CMD revealed that developmental exposure of MeHg in the larval/pupal stages can elicit graded and latent dose responses affecting adult flight behavior at lower doses (0.4-2.5 ppm in food) and eclosion (emergence from the pupa case) at higher doses (>2.5 ppm in food). The latter phenotype is accompanied by dysmorphogenesis of skeletal muscles. Here, we investigate respective roles for muscle and neural targets in MeHg toxicity. Using RNA-seq analysis, we find that developmental MeHg exposure produces 10-times as many differentially expressed transcripts in indirect flight muscle (IFM) compared to the ventral nerve cord (VNC). Among known MeHg response genes, Nrf2 antioxidant response pathway genes showed muscle-specific MeHg-induced expression changes. Within the muscle transcriptome, the most enriched and significant Gene Ontology terms identified genes required for mitochondrial ribosomal translation at the pupa stage and mitochondrial function (respiratory chain complex I) and vesicle trafficking (ESCRT III) pathways in adults, all showing decreased expression with MeHg exposure. By using an intact, whole-animal developmental model, we identify preferential candidates to evaluate a novel role for muscle-specific mitochondria and intercellular vesicular communication mechanisms as targets in MeHg toxicity and the etiology of CMD.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}